The Diagnosis: Necrolytic Acral Erythema
Histopathologic analysis of a biopsy specimen from the right leg revealed an erosion with parakeratosis containing neutrophils and marked spongiosis favoring the upper layer of the epidermis with focal individual necrotic keratinocytes. In addition, there was a lymphocytic and neutrophilic exocytosis with edema of the papillary dermal papillae, mild papillary dermal fibrosis, and a mild perivascular lymphocytic infiltrate with neutrophils and occasional eosinophils. Clinicopathologic correlation led to a diagnosis of necrolytic acral erythema (NAE).
The patient was prescribed clobetasol propionate ointment 0.05% and oral zinc sulfate 220 mg twice daily but was initially noncompliant with the topical corticosteroid regimen. He did, however, initiate zinc supplementation, which was later increased to 220 mg 3 times daily. At 3-month follow-up, the lesions had nearly completely cleared (Figure) and the serum zinc level was within reference range at 81 μg/dL.
Necrolytic acral erythema lesions had nearly completely cleared at 3-month follow-up after zinc supplementation.
Necrolytic acral erythema is a rare dermatosis that was first described in 1996 by el Darouti and Abu el Ela1 in a series of 7 Egyptian patients. Since then, most of the cases have reported concomitant hepatitis C virus (HCV) infection.2 Necrolytic acral erythema classically presents with symmetric, well-defined, hyperkeratotic plaques in an acral distribution, typically on the dorsal aspect of the feet.2,3 Lesions may involve the dorsal aspect of the toes and the lower legs, with less common involvement of the elbows, hands, and buttocks. Patients often report pruritus and/or burning.3
Abdallah et al4 proposed several stages of NAE development with erythematous papules with dusky eroded centers progressing to marginated, erythematous to violaceous, lichenified plaques. Over time, these lesions tend to thin with progressive hyperpigmentation.
Histologically, early findings of NAE include acanthosis with epidermal spongiosis and upper dermal perivascular dermatitis. Over time, lesions may exhibit psoriasiform hyperplasia with papillomatosis and parakeratosis, epidermal pallor, subcorneal pustules, vascular ectasia, papillary dermal inflammation, and necrotic keratinocytes. Minimal to moderate acanthosis with an inflammatory infiltrate may be observed later in disease progression.5
The differential diagnosis of NAE includes many benign inflammatory skin diseases. Given the acral/extensor distribution of hyperkeratotic lesions and psoriasiform pattern on histopathology, NAE initially may be misdiagnosed as psoriasis. Unlike psoriasis, however, NAE rarely involves palmoplantar skin or nails4 and may respond dramatically to treatment with zinc supplementation.6,7 Necrolytic acral erythema also may be confused with other necrolytic erythemas, including necrolytic migratory erythema, acrodermatitis enteropathica, and pellagra. A deficiency of biotin or essential fatty acids also may mimic NAE. Necrolytic acral erythema can be distinguished from these entities based on its characteristic appearance and distribution, along with comorbid HCV infection.2-4
Several reports of NAE have revealed an associated zinc deficiency.2,8 The underlying pathophysiology of zinc deficiency in NAE has not been elucidated but is thought to be related to HCV infection.2 Clinical improvement has been reported with zinc supplementation in patients with NAE at dosages of 220 mg twice daily, even in those with initial serum zinc levels within reference range.6,7 Our patient was observed to have a low serum zinc level that dramatically improved with oral supplementation.
The recognition of this uncommon entity is critical for dermatologists and dermatopathologists, as NAE has been proposed as an early cutaneous marker of HCV and may prompt the initial diagnosis of HCV.1-10 The severity of NAE has even been linked to HCV severity.1,8 Treatment of HCV has cleared NAE in several cases,4,10 implicating the virus in its pathogenesis. A proper workup for liver dysfunction and follow-up with an appropriate health care provider for HCV treatment is crucial. Our patient was encouraged to follow up with the hepatology department, as he had not been evaluated in several years.